ObjectiveTo analyze the epidemiological characteristics of long COVID and to investigate its main influencing factors by examining individuals infected with SARS-CoV-2 between March and June 2022 in two communities in Shanghai, to lay the foundation for further research on the mechanism and clinical treatment of long COVID, and to provide the basis for the development of inexpensive, convenient, and feasible prevention and intervention strategies. MethodsA cross-sectional study was conducted, enrolling 6 410 individuals infected with SARS-CoV-2. Data were collected through a questionnaire survey. The incidence and common symptoms of long COVID were analyzed, along with their associations with demographic characteristics, medical history, and behavioral factors. A logistic regression model was used to identify the major factors associated with the development of long COVID symptoms. ResultsThe overall incidence rate of long COVID among the study population was 13.9%. The most commonly reported symptoms included fatigue (65.1%), attention disorders (23.1%), and cough (16.9%). The analysis showed that having underlying chronic diseases (OR=2.580, 95%CI: 2.165‒3.074), a history of allergies (OR=1.418, 95%CI: 1.003‒1.971), current smoking (OR=1.461, 95%CI: 1.013‒2.079), ever smoking (OR=2.462, 95%CI: 1.687‒3.551), a greater number of symptoms during the acute phase [1 symptom (OR=1.778, 95%CI: 1.459‒2.162), 2 symptoms (OR=2.749, 95%CI: 2.209‒3.409), ≥3 symptoms (OR=7.792, 95%CI: 6.333‒9.593)] and aggravated symptoms during the acute phase (OR=1.082, 95%CI: 1.070‒1.094) were factors associated with a higher risk of developing long COVID symptoms. Additionally, individuals who had consumed alcohol in the past year (OR=1.914, 95%CI: 1.344‒2.684) were more prone to objective long COVID symptoms. Among individuals under 50 years of age, females (OR=1.427, 95%CI: 1.052‒1.943) were more likely to develop objective long COVID symptoms. ConclusionThis study has identified the diversity of long COVID symptoms, which involve multiple organs and systems, including fatigue, attention disorders, cough, and joint pain. It has also revealed associations between long COVID and various demographic factors (e.g., age, gender), personal medical history (e.g., underlying chronic diseases, history of allergies), acute-phase characteristics (e.g., number and severity of symptoms), and behavioral factors (e.g., smoking, alcohol consumption). These findings highlight the need for further research and ongoing surveillance of long COVID and may inform the development of more targeted health management strategies for specific populations.

Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Tumor cell-intrinsic programmed death-ligand 1 (PD-L1) signals mediate tumor initiation, progression and metastasis, but their effects in ameloblastoma (AM) have not been reported. In this comprehensive study, we observed marked upregulation of PD-L1 in AM tissues and revealed the robust correlation between elevated PD-L1 expression and increased tumor growth and recurrence rates. Notably, we found that PD-L1 overexpression markedly increased self-renewal capacity and promoted tumorigenic processes and invasion in hTERT⁺-AM cells, whereas genetic ablation of PD-L1 exerted opposing inhibitory effects. By performing high-resolution single-cell profiling and thorough immunohistochemical analyses in AM patients, we delineated the intricate cellular landscape and elucidated the mechanisms underlying the aggressive phenotype and unfavorable prognosis of these tumors. Our findings revealed that hTERT⁺-AM cells with upregulated PD-L1 expression exhibit increased proliferative potential and stem-like attributes and undergo partial epithelial‒mesenchymal transition. This phenotypic shift is induced by the activation of the PI3K-AKT-mTOR signaling axis; thus, this study revealed a crucial regulatory mechanism that fuels tumor growth and recurrence. Importantly, targeted inhibition of the PD-L1-PI3K-AKT-mTOR signaling axis significantly suppressed the growth of AM patient-derived tumor organoids, highlighting the potential of PD-L1 blockade as a promising therapeutic approach for AM.
Ameloblastoma/metabolism* ; Humans ; B7-H1 Antigen/metabolism* ; Neoplasm Recurrence, Local/pathology* ; Signal Transduction ; Cell Proliferation ; Up-Regulation ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Telomerase/metabolism* ; Jaw Neoplasms/metabolism* ; Epithelial-Mesenchymal Transition ; Animals ; Cell Line, Tumor ; Female ; Male

Objective To sort out the current situation and research hotspots of the application of information technology in drug safety in China，reveal the latest research frontier, and provide a basis for the follow-up research. Methods The literature about the application of information technology in the field of drug safety were searched from 2012 to 2022 in three major databases of CNKI, WanFang and VIP databases, and visual analysis was conducted with the help of Citespace software. Results A total of 848 valid papers were included, and the number of annual publications showed a phased growth trend, and the cooperation between authors and publishers was not close enough. The application of information technology in drug safety was mainly reflected in pharmaceutical service, intravenous drug dispensing center and antibacterial drugs. The main technical means of information construction in the field of drug safety were prescription pre-audit system, knowledge base and automation. The research frontiers were mainly intelligence, knowledge base, prescription audit, and proprietary Chinese medicines. Conclusion The application of information technology in drug safety in China is in a period of vigorous development, and cooperation among different regions, institutions, and authors should be strengthened to promote information sharing. In the future, the related research of information technology in the field of Chinese patent medicine should be focused, and the research content of information technology application in drug safety could be further improved.

Objective: To constructCSF1R+/-mice and to analyze their genotypes, so as to provide animal model basis for disease pathological mechanism and drug target. Methods : A linearized targeting vector was designed according to Cre/Loxp system. A Loxp site was inserted upstream of the 5th exon of theCSF1Rgene, and a neomycin resistance box with Loxp sites on both sides was inserted downstream of the 5th exon. The linearized targeting vector was electroporated into embryonic stem cells. The correctly targeted embryonic stem cells were injected into the blastocysts of C57BL/6J mice to obtain chimeric mice, which were bred with Zp3-Cre mice. The newborn mice were numbered 9-14 days after birth and their tails were cut. The DNA of the mice was extracted, and the genotype of the mice was identified by polymerase chain reaction and agarose gel electrophoresis. The expression of CSF1R in mouse macrophages was detected by flow cytometry. The expression of CSF1R in mouse tissues was detected by Western blot. Results: The results of agarose gel electrophoresis showed that 453 bp bands were amplified in wild type mice, and 453 bp and 650 bp bands were amplified in heterozygous mice. The results of flow cytometry showed that the expression of CSF1R in peritoneal macrophages and bone marrow-derived macrophages of CSF1R heterozygous mice was lower than that of WT group(P<0.05). The results of Western blot showed that the expression of CSF1R in spleen, kidney and brain tissue of CSF1R heterozygous group was lower than that of WT group(P<0.05). Conclusion CSF1R+/-mice are successfully constructed, reproduced and identified, which provides an animal model basis for further revealing the potential mechanism of CSF1R in immune regulation.

Rheumatoid arthritis (RA) is an autoimmune disease with a complex etiology. Monocyte-derived macrophages (MDMs) infiltration are associated with RA severity. We have reported the deletion of G-protein-coupled receptor kinase 2 (GRK2) reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling. However, as more GRK2-interacting proteins were discovered, the GRK2 interactome mechanisms in RA have been understudied. Thus, in the collagen-induced arthritis mouse model, we performed genetic GRK2 deletion using GRK2^f/fLyz2-Cre^+/- mice. Synovial inflammation and M1 polarization were improved in GRK2^f/fLyz2-Cre^+/- mice. Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptor γ (PPARγ) as a new GRK2-interacting protein. We further confirmed that fms-related tyrosine kinase 1 (Flt-1), which promoted macrophage migration to induce angiogenesis, was inhibited by GRK2-PPARγ signaling. Mechanistically, excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγ ligand-binding domain and enhanced Flt-1 transcription. Furthermore, the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology, Flt-1⁺ macrophages induced-synovial inflammation, and angiogenesis. Altogether, we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling. Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration, affording a distinct way to control joint inflammation and angiogenesis of RA.

BACKGROUND:Compared with traditional two-dimensional culture,three-dimensional microtissue culture can show greater advantages.However,more favorable cultivation methods in three-dimensional culture still need to be further explored. OBJECTIVE:To evaluate the cell behavior of microtissue and its ability to promote cartilage formation under two three-dimensional culture methods. METHODS:Cartilage-derived microcarriers were prepared by chemical decellularization and tissue crushing.DNA quantification and nuclear staining were used to verify the success of decellularization,and histological staining was used to observe the matrix retention before and after decellularization.The microcarriers were characterized by scanning electron microscopy and CCK-8 assay.Cartilage-derived microtissues were constructed by combining cartilage-derived microcarriers with human adipose mesenchymal stem cells through three-dimensional static culture and three-dimensional dynamic culture methods.The cell viability and chondrogenic ability of the two groups of microtissues were detected by scanning electron microscopy,live and dead staining,and RT-qPCR. RESULTS AND CONCLUSION:(1)Cartilage-derived microcarriers were successfully prepared.Compared with before decellularization,the DNA content significantly decreased after decellularization(P<0.001).Scanning electron microscope observation showed that the surface of the microcarrier was surrounded by collagen,maintaining the characteristics of the natural extracellular matrix of cartilage cells.CCK-8 assay indicated that microcarriers had no cytotoxicity and could promote cell proliferation.(2)Scanning electron microscopy and live and dead staining results showed that compared with the three-dimensional static group,the three-dimensional dynamic group had a more extended morphology of microtissue cells,and extensive connections between cells and cells,between cells and matrix,and between matrix.(3)The results of RT-qPCR showed that the expressions of SOX9,proteoglycan,and type Ⅱ collagen in microtissues of both groups were increased at 7 or 14 days.The relative expression levels of each gene in the three-dimensional dynamic group were significantly higher than those in the three-dimensional static group at 14 days(P<0.05).At 21 days,the three-dimensional static group had significantly higher gene expression compared with the three-diomensional dynamic group(P<0.001).(4)The results showed that compared with three-dimensional static culture microtissue,three-dimensional dynamic culture microtissue could achieve higher expression of chondrogen-related genes in a shorter time,showing better cell viability and chondrogenic ability.

Objective To understand the prevalence and risk factors of hyperuricemia in electronics factory workers in Wuhan, and to provide evidence for the health protection of electronics factory workers. Methods A total of 1 415 employees in an electronics factory in Wuhan were selected as the research subjects, and the physical examination and determination of various biochemical indicators, as well as questionnaire survey were carried out. Results The detection rate of hyperuricemia among workers in the electronics factory in Wuhan was 32.43%, with 36.33% for men and 14.11% for women, and the difference was statistically significant ( χ²＝46.077，P＜0.001). The detection rate of hyperuricemia was the highest (33.77%) among those with university or college education, followed by graduate students and above (31.50%). Compared with subjects with good lifestyle habits, people with drinking habits had higher hyperuricemia detection rate (49.38%), and the difference was statistically significant (P =0.001). The detection rates of hyperuricemia in those with central obesity and elevated alanine aminotransferase were 48.23% and 61.29%, respectively, which were significantly higher than those in the subjects without the above diseases (26.91% and 27.21%, respectively), and the differences were statistically significant (P <0.001). Obese people had the highest detection rate of hyperuricemia (66.95%), followed by overweight people (43.75%), and the difference was statistically significant (P <0.001). Multivariate logistic analysis showed that alcohol drinking (OR=1.836, 95% CI=1.139-2.961, P =0.013) and body mass index ≥ 24 kg/m² (OR=2.175, 95% CI=1.686 -2.806, P <0.001) were risk factors for hyperuricemia in electronic factory workers. Elevated alanine aminotransferase (ALT) was significantly correlated with hyperuricemia (OR=2.964, 95%CI=2.146-4.095 , P <0.001). Female gender was a protective factor for hyperuricemia in workers in the electronics factory (OR=0.441, 95%CI=0.297-0.653 , P <0.001). Conclusion The detection rate of hyperuricemia among workers in an electronics factory in Wuhan is high, and the detection rate of hyperuricemia in men is higher than that in women. Alcohol consumption, overweight and obesity will increase the risk of hyperuricemia. Elevated ALT is associated with hyperuricemia. Maintaining an ideal body mass index and establishing a good lifestyle play an important role in preventing hyperuricemia.

Objective To observe the influencing factors of early hypocalcemia after microwave ablation(MWA)for treating secondary hyperparathyroidism(SHPT).Methods Data of 82 SHPT patients who underwent MWA were retrospectively analyzed.The patients were divided into hypocalcemia group(n=36)and non-hypocalcemia group(n=46)based on presence of early hypocalcemia after MWA or not.Patients'age,gender,body mass index(BMI),dialysis method,dialysis time and number of lesions were compared between groups,so were baseline blood calcium,blood phosphorus,intact parathyroid hormone(iPTH),alkaline phosphatase(ALP),hemoglobin,albumin,creatinine,uric acid and 2 5-hydroxy vitamin D3.Logistic analysis was performed to screen the influencing factors of early hypocalcemia after MWA.Results Significant differences of dialysis methods,number of lesions,blood calcium,iPTH and ALP were found between groups(all P＜0.05).Univariate and multivariate logistic regression analysis showed that the number of lesions,iPTH and ALP were all independent influencing factors of early hypocalcemia after MWA for treating SHPT(all P＜0.05).Conclusion The number of lesions,iPTH and ALP were influencing factors of early hypocalcemia after MWA for treating SHPT.

Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (https://hlse.cn/), with the aim of synthesizing, evaluating, translating, and applying lifestyle-related evidence resources. This paper aims to introduce the functional module design of the evidence translation system, the system development process and testing, introduce the interface design and function demonstration, and explain the significance of constructing the HLSE.